A systematic study of antimicrobial properties of a toxin found in the South American wasp has allowed researchers at the Massachusetts Institute of Technology (MIT) to create variants of a peptide that can kill bacteria but doesn’t harm humans.
Insect venoms are usually plentiful in compounds that can kill bacteria, however, most of them are also toxic to humans.
Experimenting on mice, the MIT researchers found that the wasp peptide could completely eliminate Pseudomonas aeruginosa, a strain of bacteria that causes respiratory infections and is highly resistant to most antibiotics.
We’ve repurposed a toxic molecule into one that is a viable molecule to treat infections,” says Cesar de la Fuente-Nunez, a postdoc at MIT and lead author of this study. “By systematically analyzing the structure and function of these peptides, we’ve been able to tune their properties and activity.”
The peptide in question is small, only 12 amino acids long. This made it easy for the researchers to engineer variants of it and test them on humans.
“It’s a small enough peptide that you can try to mutate as many amino acid residues as possible to try to figure out how each building block is contributing to antimicrobial activity and toxicity,” de la Fuente-Nunez says.
Like other antimicrobial peptides, this venom derived amino acid chain is believed to kill microbes by disrupting bacterial cell membranes. It also has an alpha helical structure which is known to react strongly with cell membranes.
Initially, researchers created a few dozen variants and then measured how their changes affected the peptide’s helical structure and its hydrophobicity. This helped determine how well the peptides would interact with cell membranes. They then tested these peptides against seven strains of bacteria and two of fungus, making it possible to correlate their structure and physicochemical properties with their antimicrobial potency.
The researchers then designed a few dozen more peptides based on their findings, eventually finding the most optimal compositions for the peptide.
Researchers then exposed the engineered peptides to human embryonic kidney cells grown in a petri dish. Here, they chose the most promising compounds to test in mice infected with Pseudomonas aeruginosa. Many of them significantly reduced the presence of the infection, but ultimately chose the one which eliminated it completely.
“After four days, that compound can completely clear the infection, and that was quite surprising and exciting because we don’t typically see that with other experimental antimicrobials or other antibiotics that we’ve tested in the past with this particular mouse model,” said de la Fuente-Nunez.
Researchers have begun creating variants of the peptide which they hope will be able to clear infections in lower doses.